Antiproliferative Effect of Beauvericin on Retinoblastoma

Beauvericin對於視網膜母細胞瘤抑制作用之研究

鄭成國(Cheng-Kuo Cheng) ； 張凱鈞(Kai-Chun Chang) ； 李憶菁(Yih-Jing Lee)

《輔仁醫學期刊》 7卷4期 (2009/12) Pp. 161-169

摘要

背景和目的：視網膜母細胞瘤是最常見的兒童惡性腫瘤，大約每20000名兒童就會有一名發病，該疾病的存活率大約只有50%左右，因此研發此疾病的有效治療方法即是一個重要的課題。多項研究報告指出beauvericin可以藉由影響肺部細胞的離子平衡，進而有抑制人類肺癌細胞的生長的效果。因此我們利用此特性，進一步研究beauvericin治療視網膜母細胞瘤的可能性。方法：我們培養人類視網膜母細胞瘤細胞株並且利用MTT檢測來觀察不同濃度的beauvericin對於細胞活性的抑制效果。進一步藉由觀察細胞內的去氧核醣核酸片段形成的程度，以及流質細胞技術來研究beauvericin對於細胞凋亡的影響。另一方面，我們也將人類視網膜母細胞瘤細胞株移植到裸鼠的體內，來研究beauvericin對於癌細胞的體內抑制作用。結果：體外實驗證明beauvericin可以有效降低視網膜母細胞瘤細胞的存活率，並且增加細胞凋亡的發生率。另一方面，流質細胞技術研究也發現beauvericin可以促進視網膜母細胞瘤的細胞停留在細胞週期的G0/G1階段。動物實驗結果更進一步證明beauvericin於體內也有降低腫瘤的發生率以及降低腫瘤細胞大小的效果。結論：Beauvericin提供一種可能可以有效治療視網膜母細胞瘤的選擇。（輔仁醫學期刊2009; 7 (4): 161-169）

關鍵字

beauvericin ； 視網膜 ； 視網膜母細胞瘤 ； 去氧核醣核酸片段 ； 細胞凋亡 ； 流質細胞儀

並列摘要

Background and purpose: Retinoblastoma is a malignant tumor of the retina that usually occur in young children. They are the most common pediatric tumor and have an incidence of approximately 1 in 20,000 children. Advanced retinoblastoma disease is correlated with poor patient survival, and survival rates for extraocular disease range 0%~50%. It is therefore very important to find an effective therapy for this disease. Beauvericin is a mycotoxin produced by several Fusarium species. Several studies reported that beauvericin can modulate ionic homeostasis and shows inhibitory effects on lung cancer cell growth. We therefore used beauvericin to treat retinoblastoma cells to investigate the antiproliferative effect on these cells. Methods: An MTT test was used to detect the cell viability after treatment with beauvericin. DNA fragments in apoptotic cells were also examined and counted after treatment. The effect of beauvericin on altering the cell cycle in retinoblastoma cells was studied via flow cytometry. Results: Beauvericin reduced the cell viability of retinoblastoma cells and increased the percentage of cells in the sub-G0/G1 phase. It was also found that beauvericin increased the DNA fragmentation of retinoblastoma cells. The in vivo antiproliferative effect of beauvericin was also detected using a retinoblastoma cell-transplanted null mouse animal model. The results indicated that beauvericin reduced the occurrence of tumor formation and tumor size in this animal model. Conclusions: Beauvericin provides a possibly effective therapeutic choice for treating retinoblastomas. (FJJM 2009; 7 (4): 161-169)

並列關鍵字

beauvericin ； retina ； retinoblastoma ； DNA fragmentation ； cell apoptosis ； flow cytometry